Efficacy and Safety of MK-8189 in Participants With an Acute Episode of Schizophrenia (MK-8189-008)
- Conditions
- Interventions
- Registration Number
- NCT04624243
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of MK-8189 at a range of doses (8 mg, 16 mg, and 24 mg once daily) in adult participants who have an acute episode of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria. The primary hypotheses are the following: (1) MK-8189 24 mg is sup...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 500
The main inclusion criteria include, but are not limited to the following:
- Meet the diagnostic criteria for schizophrenia according to the DSM-5
- Have an illness duration for schizophrenia of at least 1 year
- Be confirmed to be experiencing an acute episode of schizophrenia as evidenced by ALL of the following: (a) onset of the current acute episode is ≤6 weeks before screening (b) current symptoms represent a marked and substantial worsening compared with the participant's usual symptomatic state prior to the current acute episode, and are associated with diminished functional ability (c) in need of increased psychiatric attention to treat worsening acute episode symptoms
- Have a CGI-S score of ≥4 (moderately ill) at screening and baseline
- Have an identified responsible person referred to as the "external contact person" who has agreed to provide information about the participant's location if needed during outpatient portion of the study. The site personnel must consider this identified responsible person a reliable contact person, and the contact person must have regular contact with the participant (defined at screening as direct contact no fewer than 3 times per week), and with the expectation that this frequency of contact would continue (either in person or via other contact method), throughout duration of the study, including the follow-up period)
The main exclusion criteria include, but are not limited to the following:
- Has a primary current diagnosis other than schizophrenia or a comorbid diagnosis that is primarily responsible for the current symptoms and functional impairment
- Meets criteria for moderate to severe substance use disorder within past 6 months prior to screening (excluding those related to caffeine or nicotine)
- Has a known history of the following: (a) borderline personality disorder, anti-social personality disorder, or bipolar disorder (b) traumatic brain injury causing ongoing cognitive difficulties, Alzheimer's Disease, or another form of dementia, or any chronic organic disease of the central nervous system (c) intellectual disability of a severity that would impact ability to participate in the study
- Has a current diagnosis of a psychotic disorder other than schizophrenia or a behavioral disturbance thought to be due to substance abuse
- Is or was under involuntary commitment for the acute episode, because the participant is considered a danger to themselves or others
- Has a history of treatment resistance exhibited by any of the following: (a) no or minimal response to at least 2 periods of treatment lasting 6 weeks or longer, with antipsychotic agents at the maximally tolerated dose. Participants who have responded to antipsychotics only when paired with clozapine are considered treatment-resistant (b) history of electroconvulsive therapy (ECT) treatment for treatment-resistant schizophrenia within the past 6 months (c) past or current use of clozapine as single or adjunctive therapy for schizophrenia within the past 3 months
- Is currently participating in or has participated in another clinical study and received an experimental or investigational drug agent within 3 months prior to screening visit of this current study and has participated in no more than 2 studies in the past 2 years
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MK-8189 8 mg (Acute) - MK-8189 8 mg (Extension) MK-8189 Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 8 mg once daily (QD) in the acute treatment period from Week 1-6 followed by MK-8189 8 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. Enrollment of participants in the MK-8189 8 mg arm was closed with Amendment 4. Participants enrolled before Amendment 4 that have been assigned to 8 mg MK-8189 will remain on 8 mg MK-8189 per protocol. MK-8189 24 mg (Acute) - MK-8189 24 mg (Extension) Placebo to risperidone Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 24 mg QD in the acute treatment period from Week 1-6 followed by MK-8189 24 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. Placebo to MK-8189 (Acute) - MK-8189 24 mg (Extension) MK-8189 Participants will be treated for a total of 12 weeks. Participants will receive MK-8189-matching placebo QD in the acute treatment period from Week 1-6 followed by MK-8189 24 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. Placebo to MK-8189 (Acute) - MK-8189 24 mg (Extension) Placebo to MK-8189 Participants will be treated for a total of 12 weeks. Participants will receive MK-8189-matching placebo QD in the acute treatment period from Week 1-6 followed by MK-8189 24 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. MK-8189 24 mg (Acute) - MK-8189 24 mg (Extension) MK-8189 Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 24 mg QD in the acute treatment period from Week 1-6 followed by MK-8189 24 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. MK-8189 16 mg (Acute) - MK-8189 16 mg (Extension) Placebo to risperidone Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 16 mg QD in the acute treatment period from Week 1-6 followed by MK-8189 16 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. Placebo to MK-8189 (Acute) - MK-8189 24 mg (Extension) Placebo to risperidone Participants will be treated for a total of 12 weeks. Participants will receive MK-8189-matching placebo QD in the acute treatment period from Week 1-6 followed by MK-8189 24 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. MK-8189 8 mg (Acute) - MK-8189 8 mg (Extension) Placebo to risperidone Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 8 mg once daily (QD) in the acute treatment period from Week 1-6 followed by MK-8189 8 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. Enrollment of participants in the MK-8189 8 mg arm was closed with Amendment 4. Participants enrolled before Amendment 4 that have been assigned to 8 mg MK-8189 will remain on 8 mg MK-8189 per protocol. MK-8189 16 mg (Acute) - MK-8189 16 mg (Extension) MK-8189 Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 16 mg QD in the acute treatment period from Week 1-6 followed by MK-8189 16 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. Risperidone 6 mg (Acute) - Risperidone 6 mg (Extension) Risperidone Participants will be treated for a total of 12 weeks. Participants will receive risperidone 6 mg QD in the acute treatment period from Week 1-6 followed by risperidone 6 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive MK-8189-matching placebo QD from Week 1-12. Risperidone 6 mg (Acute) - Risperidone 6 mg (Extension) Placebo to MK-8189 Participants will be treated for a total of 12 weeks. Participants will receive risperidone 6 mg QD in the acute treatment period from Week 1-6 followed by risperidone 6 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive MK-8189-matching placebo QD from Week 1-12.
- Primary Outcome Measures
Name Time Method Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo Baseline, Week 6 The PANSS assesses the severity of schizophrenia symptoms through a 30-item clinician-rated inventory organized into a positive subscale (7 items), a negative subscale (7 items) and a general psychopathology subscale (16 items). For each item, symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS total score for each participant wil...
Number of participants who discontinue study treatment due to an AE ~Up to Week 12 An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention.
Number of participants who experience one or more adverse events (AEs) ~Up to Week 14 An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention.
- Secondary Outcome Measures
Name Time Method Change from baseline in PANSS positive subscale (PSS) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo Baseline, Week 6 The PANSS Positive Subscale (PSS) assesses the severity of schizophrenia symptoms and the PANSS PSS score for each participant will be calculated as the sum of the rating assigned to each of the 7 PSS items and will range from 7 (lowest total score) to 49 (highest total score). Higher scores reflect more severe symptoms of schizophrenia.
Change from baseline in Clinical Global Impression-Severity of Illness (CGI-S) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo Baseline, Week 6 The CGI-S is a single item 7-point clinician rated scale for assessing the global severity of the participant's illness. CGI-S scores range from 1 (participant normal, not ill) to 7 (participant extremely ill). A decrease in the CGI-S score indicates reduced severity of the participant's illness.
Change from baseline in weight at Week 12: MK-8189 24 mg, MK-8189 16 mg, or risperidone Baseline, Week 12 Body weight will be measured using a standardized scale.
Change from baseline in weight at Week 6: MK-8189 24 mg, MK-8189 16 mg, MK-8189 8 mg or placebo Baseline, Week 6 Body weight will be measured using a standardized scale.
Trial Locations
- Locations (121)
Pillar Clinical Research, LLC ( Site 1038)
🇺🇸Chicago, Illinois, United States
Richmond Behavioral Associates ( Site 1064)
🇺🇸Staten Island, New York, United States
Massachusetts General Hospital ( Site 1035)
🇺🇸Boston, Massachusetts, United States
CITRIALS ( Site 1010)
🇺🇸Bellflower, California, United States
Collaborative Neuroscience Research, LLC ( Site 1041)
🇺🇸Garden Grove, California, United States
Woodland International Research Group, LLC ( Site 1002)
🇺🇸Little Rock, Arkansas, United States
ProScience Research Group ( Site 1046)
🇺🇸Culver City, California, United States
Behavioral Research Specialists, LLC ( Site 1032)
🇺🇸Glendale, California, United States
CITRIALS ( Site 1016)
🇺🇸Riverside, California, United States
Behavioral Clinical Research ( Site 1058)
🇺🇸Hollywood, Florida, United States
Schuster Medical Research Institute ( Site 1023)
🇺🇸Sherman Oaks, California, United States
Behavioral Clinical Research , Inc ( Site 1013)
🇺🇸Miami Lakes, Florida, United States
Research Centers of America ( Hollywood )-Central Nervous System (CNS) ( Site 1065)
🇺🇸Hollywood, Florida, United States
Fort Lauderdale Behavioral Health Center ( Site 1028)
🇺🇸Oakland Park, Florida, United States
Health Synergy Clinical Research ( Site 1051)
🇺🇸Stuart, Florida, United States
Atlanta Center For Medical Research ( Site 1022)
🇺🇸Atlanta, Georgia, United States
CenExel iResearch, LLC ( Site 1039)
🇺🇸Decatur, Georgia, United States
Uptown Research Institute ( Site 1052)
🇺🇸Chicago, Illinois, United States
Ascension Saint Elizabeth ( Site 1000)
🇺🇸Chicago, Illinois, United States
CBH Health ( Site 1044)
🇺🇸Gaithersburg, Maryland, United States
Arch Clinical Trials ( Site 1048)
🇺🇸Saint Louis, Missouri, United States
New Hope Clinical Research ( Site 1050)
🇺🇸Charlotte, North Carolina, United States
Midwest Clinical Research ( Site 1059)
🇺🇸Dayton, Ohio, United States
Midwest Clinical Research Center ( Site 1033)
🇺🇸Dayton, Ohio, United States
Neuro-Behavioral Clinical Research ( Site 1055)
🇺🇸North Canton, Ohio, United States
Community Clinical Research ( Site 1057)
🇺🇸Austin, Texas, United States
Pillar Clinical Research, LLC ( Site 1004)
🇺🇸Richardson, Texas, United States
Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD ( Site 3002)
🇧🇬Burgas, Bulgaria
State Psychiatric Hospital "Sv. Ivan Rilski", Novi Iskar ( Site 3001)
🇧🇬Novi Iskar, Sofia, Bulgaria
Center for Mental Health Prof. Nikola Shipkovenski Ltd ( Site 3000)
🇧🇬Sofia, Bulgaria
Kohnodai Hospital, National Center for Global Health and Medicine ( Site 2005)
🇯🇵Ichikawa, Chiba, Japan
Wakato Hospital ( Site 2031)
🇯🇵Kitakyushu, Fukuoka, Japan
Soushu Hospital ( Site 2008)
🇯🇵Atsugi, Kanagawa, Japan
Komoro Kogen Hospital ( Site 2046)
🇯🇵Komoro, Nagano, Japan
Amekudai Hospital ( Site 2020)
🇯🇵Naha, Okinawa, Japan
National Hospital Organization Hizen Psychiatric Medical Center ( Site 2017)
🇯🇵Kanzaki-gun, Saga, Japan
Rainbow and Sea Hospital ( Site 2016)
🇯🇵Karatsu, Saga, Japan
Inokuchi Noma Hospital ( Site 2030)
🇯🇵Fukuoka, Japan
Chiba University Hospital ( Site 2024)
🇯🇵Chiba, Japan
Nishigahara Hospital ( Site 2042)
🇯🇵Kita-ku, Tokyo, Japan
National Center of Neurology and Psychiatry ( Site 2023)
🇯🇵Kodaira, Tokyo, Japan
Kuramitsu Hospital ( Site 2014)
🇯🇵Fukuoka, Japan
Seijin Hospital ( Site 2026)
🇯🇵Tokyo, Japan
Inje University Busan Paik Hospital ( Site 0604)
🇰🇷Busan, Pusan-Kwangyokshi, Korea, Republic of
Seoul National University Hospital ( Site 0600)
🇰🇷Seoul, Korea, Republic of
Specjal. Psychiatryczny ZOZ w Lodzi, Szpital im. Babinskiego ( Site 0905)
🇵🇱Lodz, Lodzkie, Poland
Klinika Psychiatryczna Wydzialu Nauki o Zdrowiu WUM ( Site 0900)
🇵🇱Pruszkow, Mazowieckie, Poland
Piejuras Slimnica Psihiatriska Klinika ( Site 8001)
🇱🇻Liepaja, Latvia
Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0816)
🇷🇴Bucharest, Bucuresti, Romania
Institutul de Psihiatrie Socola ( Site 0810)
🇷🇴Iași, Iasi, Romania
Moscow Scientific Research Institute for Psychiatry ( Site 6013)
🇷🇺Moscow, Moskva, Russian Federation
SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6001)
🇷🇺St. Petersburg, Sankt-Peterburg, Russian Federation
SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6000)
🇷🇺St. Petersburg, Sankt-Peterburg, Russian Federation
Central Moscow Regional Clinical Psychiatric Hospital ( Site 6018)
🇷🇺Moscow, Moskva, Russian Federation
SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6002)
🇷🇺St. Petersburg, Sankt-Peterburg, Russian Federation
Clinical Center of Serbia ( Site 5101)
🇷🇸Belgrade, Beograd, Serbia
Stavropol Region Psychiatric Hospital #2 ( Site 6005)
🇷🇺Stavropol, Stavropol Skiy Kray, Russian Federation
Federal State Scientific Institution Research Institute of Mental Health ( Site 6014)
🇷🇺Tomsk, Tomskaya Oblast, Russian Federation
Clinical Center of Serbia ( Site 5107)
🇷🇸Belgrade, Beograd, Serbia
Institut za mentalno zdravlje ( Site 5105)
🇷🇸Belgrade, Beograd, Serbia
University Clinical Hospital Center "Dr. Dragisa Misovic - Dedinje" ( Site 5104)
🇷🇸Belgrade, Beograd, Serbia
Clinical Center Kragujevac ( Site 5100)
🇷🇸Kragujevac, Sumadijski Okrug, Serbia
Clinical Center Kragujevac ( Site 5106)
🇷🇸Kragujevac, Sumadijski Okrug, Serbia
China Medical University Hospital ( Site 9006)
🇨🇳Taichung, Taiwan
Taipei City Hospital, Songde Branch ( Site 9004)
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital - Linkou Branch ( Site 9002)
🇨🇳Taoyuan, Taiwan
CNE "Precarpathian Regional Clinical Center of Mental Health of Ivano-Frankivsk Regional Council"" (
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
CNE of Kharkiv Reg. Council Reg. Clinical Psychiatric Hospital Nub 3 ( Site 7012)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine
Institute of Neurology,Psychiatry and Narcology AMS Ukraine ( Site 7011)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine
CNE Clinical Hospital PSYCHIATRY of executive body of Kyiv City Council -Kyiv City State Admin ( Sit
🇺🇦Kyiv, Kyivska Oblast, Ukraine
CNE. Kherson Regional Psychiatric Hospital ( Site 7004)
🇺🇦Kherson, Khersonska Oblast, Ukraine
Mental Health Center - Veliko Tarnovo ( Site 3006)
🇧🇬Veliko Tarnovo, Bulgaria
Kanagawa Psychiatric Center ( Site 2035)
🇯🇵Yokohama-Shi, Kanagawa, Japan
Klinicki bolnicki centar Rijeka ( Site 4005)
🇭🇷Rijeka, Primorsko-goranska Zupanija, Croatia
Tanzawa Hospital ( Site 2037)
🇯🇵Hadano, Kanagawa, Japan
Institutul de Psihiatrie Socola ( Site 0814)
🇷🇴Iași, Iasi, Romania
Arkhangelsk Regional Psychiatric Clinical Hospital ( Site 6020)
🇷🇺Arkhangelsk, Arkhangel Skaya Oblast, Russian Federation
Lipetsk Regional Psychoneurology Hospital ( Site 6021)
🇷🇺Lipetsk, Lipetskaya Oblast, Russian Federation
State Psychiatric Hospital - Kardzhali ( Site 3005)
🇧🇬Kardzhali, Bulgaria
Woodland Research Northwest, LLC ( Site 1036)
🇺🇸Rogers, Arkansas, United States
Klinika za psihijatriju Vrapce ( Site 4000)
🇭🇷Zagreb, Grad Zagreb, Croatia
Klinika za psihijatriju Vrapce ( Site 4001)
🇭🇷Zagreb, Grad Zagreb, Croatia
Klinika za psihijatriju Sveti Ivan ( Site 4003)
🇭🇷Zagreb, Zagrebacka Zupanija, Croatia
Shiranui Hospital ( Site 2043)
🇯🇵Omuta, Fukuoka, Japan
Benchmark Research ( Site 1054)
🇺🇸Shreveport, Louisiana, United States
Seishinkai Okehazama Hospital Fujita Kokoro Care Center ( Site 2011)
🇯🇵Toyoake, Aichi, Japan
Yuge Hospital ( Site 2018)
🇯🇵Kumamoto, Japan
Samodzielny Wojewódzki Zespół Publicznych Zakładów Psychiatrycznej Opieki Zdrowotnej w Warszawie ( S
🇵🇱Warsaw, Mazowieckie, Poland
Uniwersyteckie Centrum Kliniczne ( Site 0902)
🇵🇱Gdansk, Pomorskie, Poland
Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0818)
🇷🇴Bucharest, Bucuresti, Romania
SGHI Leningrad Region Psyconeurology Dispensary ( Site 6017)
🇷🇺Leningrad Region, Leningradskaya Oblast, Russian Federation
Psychiatric Clinical Hospital 4 named after PB Gannushkin ( Site 6016)
🇷🇺Moscow, Moskva, Russian Federation
Yaroslavl Regional Clinical Psychiatry Hospital ( Site 6022)
🇷🇺Yaroslavl, Yaroslavskaya Oblast, Russian Federation
Pillar Clinical Research ( Site 1047)
🇺🇸Bentonville, Arkansas, United States
Hassman Research Institute Marlton Site ( Site 1040)
🇺🇸Marlton, New Jersey, United States
Seimou Hospital ( Site 2004)
🇯🇵Tomioka, Gunma, Japan
National Hospital Organization Ryukyu Hospital ( Site 2019)
🇯🇵Kunigamigun, Okinawa, Japan
Narimasu Kosei Hospital ( Site 2006)
🇯🇵Tokyo, Japan
Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0815)
🇷🇴Bucharest, Bucuresti, Romania
Bekhterev Research Institute for Psychoneurology ( Site 6008)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Ongata Hospital ( Site 2007)
🇯🇵Hachioji, Tokyo, Japan
Daugavpils Psihoneirologiska Slimnica ( Site 8005)
🇱🇻Daugavpils, Latvia
Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0817)
🇷🇴Bucharest, Bucuresti, Romania
Centrum Medyczne HCP ( Site 0913)
🇵🇱Poznań, Wielkopolskie, Poland
Psychiatric Clinical Hospital 4 named after PB Gannushkin-Psychiatric department 4 ( Site 6023)
🇷🇺Moscow, Moskva, Russian Federation
Clinical Center Kragujevac ( Site 5102)
🇷🇸Kragujevac, Sumadijski Okrug, Serbia
Special Hospital for Psychiatric Diseases Kovin ( Site 5108)
🇷🇸Kovin, Vojvodina, Serbia
Special Hospital for Psychiatric Diseases Kovin ( Site 5109)
🇷🇸Kovin, Vojvodina, Serbia
Taipei Veterans General Hospital ( Site 9000)
🇨🇳Taipei, Taiwan
Kyiv City Psychoneurological Hospital 2 ( Site 7008)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
National Taiwan University Hospital ( Site 9001)
🇨🇳Taipei, Taiwan
Dnepropetrovsk Regional Clinical Hospital Mechnikov-Regional Centre of Psychosomatic Disorders base
🇺🇦Dnipro, Dnipropetrovska Oblast, Ukraine
CNE "Vinnytsia Regional Clinical Psycho-neurological hospita-Mixed (men and women) department #2 ( S
🇺🇦Vinnytsya, Vinnytska Oblast, Ukraine
CNE Cherkasy reg. psychiatric hospital of Cherkasy regional council ( Site 7009)
🇺🇦Smila, Cherkaska Oblast, Ukraine
MNE of KRC-Regional psychiatric and narcological medical association ( Site 7005)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
Mental Health Center - Ruse, EOOD ( Site 3003)
🇧🇬Ruse, Bulgaria
Artemis Institute for Clinical Research ( Site 1019)
🇺🇸San Diego, California, United States
California Neuropsychopharmacology Clinical Research Institute, LLC (CNRI-San Diego, LLC) ( Site 103
🇺🇸San Diego, California, United States
Premier Clinical Research Institute ( Site 1049)
🇺🇸Miami, Florida, United States
Altea Research Institute ( Site 1012)
🇺🇸Las Vegas, Nevada, United States
Kyungpook National University Hospital ( Site 0601)
🇰🇷Daegu, Taegu-Kwangyokshi, Korea, Republic of